LC-MS/MS法研究盐酸曲美他嗪片的人体药动学及生物等效性  

Bioequivalence and pharmacokinetic study of trimetazidine dihydrochloride in human plasma by using LC-MS/MS

作　　者：张峻颖[1] 杨洁 熊守军 刘赛 曹艺[3] 邓书岚 吴春勇[3] 陈沄[4] 

机构地区：[1]中国药科大学中药制剂教研室,南京211198 [2]南京生命能科技开发有限公司,南京210016 [3]中国药科大学药物分析教研室,南京210009 [4]中国医学科学院皮肤病研究所,南京210042

出　　处：《中国新药杂志》2013年第21期2519-2523,共5页Chinese Journal of New Drugs

摘　　要：目的：建立LC—MS／MS法测定人血浆曲美他嗪浓度，研究2种盐酸曲美他嗪片的人体药动学和生物等效性。方法：采用随机、双周期交叉试验设计，20名健康受试者单剂量口服20mg受试制剂和参比制剂后不同时间点的血浆样品经10％三氯乙酸水溶液沉淀蛋白，采用LC-MS／MS法测定曲美他嗪的血药浓度，计算药动学参数和相对生物利用度，评价2种制剂的生物等效性。结果：本方法在0.05～200 ng·mL^-1 范围内线性关系良好，最低定量限为0.05 ng·mL^-1，绝对回收率为89.02～93.75％，精密度和准确度均符合要求。盐酸曲美他嗪受试制剂和参比制剂的Cmax分别为（50.98±9.65）和（50.53±8.98） ng·mL^-1；Tmax分别为（1.5±0.4）和（1.5±0.3）h;t1／2分别为（5.89±0.47）和（5.77±0.56）h；AUC0～24分别为（390.75±91.55）和（379.90±84.13）ng·mL^-1·h。受试制剂对参比制剂的相对生物利用度为（102.8±7.5）％。结论：本方法灵敏度高，样品处理简便快速。测得的受试制剂和参比制剂的主要药动学参数经统计学检验无显著性差异，表明2种制剂在人体内生物等效。Objective： To determine trimetazidine in human plasma by LC-MS/MS method, and to investigate its pharmacokinetics and bioequivalence. Methods： A two-way crossover study was adopted and the test and reference formulations containing 20 mg trimetazidine dihydrochloride were administered to 20 healthy male volunteers, respectively. Plasma concentrations were analyzed by a validated LC-MS/MS method after precipitated by addition of 10% trichloracetic acid solution. The pharmacokinetic parameters were calculated and bioequivalence was evaluated. Results ： The calibration curve was linear in the range over 0.05～200 ng·mL-1 with LLOQ of 0.05 ng·mL-1. Absolute recovery was 89.02～93.75%. Accuracy and precision were conformed to fit the requirement. The pharmacokinetic parameters for the test and reference tablets were as follows ： Cmax were （50.98±9.65） and （50.53±8.98） ng·mL^-1, Tmax were （1.5±0.4） and （1.5±0.3） h, t1/2 were （5.89±0.47） and （5.77±0.56）h, and AUC0-24 were （390.75±91.55 ） and （ 379.90±84.13 ） ng·mL^-1. h, respectively. Relative bioavailability was （102.8±7.5）%. Conclusion： The method is sensitive and convenient. No significant differenceis observed among the main pharmacokinetic parameters of the test and reference tablets, demonstrating that the two formulations are bioequivalent.

关 键 词：盐酸曲美他嗪 LC—MS MS 药动学 生物等效性 

分 类 号：R932[医药卫生—生药学]